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Association study of tryptophan hydroxylase 2 gene polymorphisms in bipolar disorder patients with panic disorder comorbidity

Campos, Simone Bechoa; Miranda, Débora M.a; Souza, Bruno R.c; Pereira, Patricia A.a; Neves, Fernando S.a; Tramontina, Julianab; Kapczinski, Fláviob; Romano-Silva, Marco Aurélioa; Correa, Humbertoa,d

doi: 10.1097/YPG.0b013e328341a3a8
Brief Reports

Frequent comorbidity between panic disorder (PD) and mood disorders has been widely reported in clinical and epidemiological studies and, recently, an increasing attention has been paid to the cooccurrence of PD and bipolar disorder (BD). Several studies have shown that an imbalance of serotonin activity could be related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible candidates for the association with PD. The aim of this study is to investigate a possible association between TPH2 gene polymorphisms and the PD comorbidity susceptibility.Our sample consisted of 515 patients; 274 patients with BD (subtypes I and II), including 45 patients with lifetime panic disorder comorbidity and 241 controls. These patients were genotyped for eight tagging single nucleotide polymorphisms of the gene of human TPH2. We found significant differences between patients with BD, with panic disorder comorbidity, and controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359; rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731, P=0.011; rs4760820, P=0.0259). We also identified significant differences between patients with BD, with and without panic disorder comorbidity in the allelic analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820, P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357, P=0.052). The haplotype analysis in the group of patients with BD, with and without panic disorder comorbidity, was also significant (rs4448731-rs4565946, P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further studies are needed to replicate the positive association that we observed.

aInstituto Nacional de Ciência e Tecnologia de Medicina Molecular, Laboratório de Neurociências e Genética Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais

bPrograma de Transtorno Bipolar e Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, Porto Alegre, Rio Grande do Sul, Brazil

cDepartment of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada

dCentre of Psychiatry and Neuroscience, Paris Descartes University, INSERM, U894, Sainte-Anne Hospital, Paris, France

Correspondence to Simone Becho Campos, MD, Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Laboratório de Neurociências e Genética Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena 190, 30130-100, Belo Horizonte, MG, Brazil Tel: +55 31 34099650; fax: +55 31 34099134; e-mail: simonebecho@gmail.com

Received March 5, 2010

Accepted August 24, 2010

© 2011 Lippincott Williams & Wilkins, Inc.